Ronenn Roubenoff

Ronenn Roubenoff
Novartis Institutes for BioMedical Research | NIBR · Translational Medicine

MD, MHS

About

365
Publications
72,831
Reads
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31,396
Citations
Introduction
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Additional affiliations
January 2010 - present
Novartis Institutes for BioMedical Research
Position
  • Global Head, Musculoskeletal Translational Medicine
January 2006 - October 2009
Position
  • Biogen Idec
January 2006 - September 2009
Biogen Idec
Position
  • Sr. Director

Publications

Publications (365)
Article
Background and objectives Limited data suggests that quantitative MRI (qMRI) measures have potential to be used as trial outcome measures in sporadic inclusion body myositis (sIBM), and as a non-invasive assessment tool to study sIBM muscle pathological processes. Our aim was to evaluate changes in muscle structure and composition using a comprehen...
Article
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Objective: To determine whether a multicomponent intervention based on physical activity with technological support and nutritional counselling prevents mobility disability in older adults with physical frailty and sarcopenia. Design: Evaluator blinded, randomised controlled trial. Setting: 16 clinical sites across 11 European countries, Janua...
Article
Biomedical research accuracy and relevance for improving healthcare are increasingly identified as costly problems. Basic research data quality, reporting and methodology, and reproducibility are common factors implicated in this challenge. Preclinical models of disease and therapy, largely conducted in rodents, have known deficiencies in replicati...
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Background LNA043 is a modified, recombinant version of the human angiopoietin-like 3 (ANGPTL3) protein acting directly on cartilage-resident cells to transmit its cartilage anabolic effect. A first-in-human study previously demonstrated the favourable safety profile and the modulation of several pathways involved in cartilage homeostasis and osteo...
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Background Rotator cuff tendinopathy (RC TP) is a multifactorial condition and one of the most common causes of musculoskeletal burden. Current standard of care (SoC) is limited to pain relief with NSAIDs and physiotherapy. Recent evidence indicates that IL-17A-expressing tendon-resident immune cells are present in human overuse tendinopathy, and I...
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Importance Antibody blockade of activin type II receptor (ActRII) signaling stimulates skeletal muscle growth. Previous clinical studies suggest that ActRII inhibition with the monoclonal antibody bimagrumab also promotes excess adipose tissue loss and improves insulin resistance. Objective To evaluate the efficacy and safety of bimagrumab on body...
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Background Bimagrumab prevents activity of myostatin and other negative regulators of skeletal muscle mass. This randomized double‐blind, placebo‐controlled study investigated safety, pharmacokinetics (PK), and pharmacodynamics of bimagrumab in healthy older and obese adults. Methods A cohort of older adults (aged 70–85 years) received single intr...
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Health care has had to adapt rapidly to COVID-19, and this in turn has highlighted a pressing need for tools to facilitate remote visits and monitoring. Digital health technology, including body-worn devices, offers a solution using digital outcomes to measure and monitor disease status and provide outcomes meaningful to both patients and health ca...
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Importance The potential benefit of novel skeletal muscle anabolic agents to improve physical function in people with sarcopenia and other muscle wasting diseases is unknown. Objective To confirm the safety and efficacy of bimagrumab plus the new standard of care on skeletal muscle mass, strength, and physical function compared with standard of ca...
Article
Background: Osteoarthritis is a common inflammatory disorder with no disease-modifying therapies. Whether inhibition of interleukin-1β (IL-1β) can reduce the consequences of large joint osteoarthritis is unclear. Objective: To determine whether IL-1β inhibition with canakinumab reduces incident total hip or knee replacement (THR/TKR). Design:...
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Background Digital technologies and advanced analytics have drastically improved our ability to capture and interpret health-relevant data from patients. However, only limited data and results have been published that demonstrate accuracy in target indications, real-world feasibility, or the validity and value of these novel approaches. Objective...
Article
Sarcopenia, the associated loss of skeletal muscle mass and strength and impaired physical function seen with aging, is a growing, global public health challenge in need of accepted, proven treatments that address the needs of a broad range of older adults. While exercise, primarily resistance training, and increased dietary protein have been shown...
Article
475 LONGITUDINAL ASSESSMENT OF CARTILAGE COMPOSITION BY HIGH-FIELD MRI IN PATIENTS WITH LOW-GRADE KNEE CARTILAGE INJURY C. Scotti 1, D. Laurent 1, V. Juras 2, V. Mlynarik 2, M. Schreiner 2, P. Szomolanyi 2, S. Zbyn 2, J. Goldhahn 3, H. Haber 1, E. Kubiak 1, R. Roubenoff 1, S. Marlovits 4, M. Schieker 1, S. Trattnig 2. 1 Novartis Inst. for BioMed. R...
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The colony-stimulating factor-1 (CSF-1) receptor pathway has been implicated in a variety of diseases, and CSF-1-dependent mechanisms are also involved in bloodborne protein clearance. Lacnotuzumab is a novel, high-affinity, humanized, anti-CSF-1 monoclonal antibody that prevents CSF-1-mediated receptor activation. This phase 1, two-part, double-bl...
Article
The impressive increase in lifespan that occurred in the 20th century has driven a boom in age-associated degeneration resulting from senescence. Geriatric syndromes such as sarcopenia and frailty do not fall neatly into classical medical definitions of disease because they result from subtle declines in physiological function that occur over many...
Article
Background: Spinal and bulbar muscular atrophy is an X-linked neuromuscular disease caused by CAG repeat expansion in the androgen receptor gene. Patients with this disease have low concentrations of insulin-like growth factor-1 (IGF-1), and studies of overexpression and administration of IGF-1 showed benefit in a transgenic model; thus the IGF-1...
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Background: The ongoing "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies (SPRINTT)" randomized controlled trial (RCT) is testing the efficacy of a multicomponent intervention in the prevention of mobility disability in older adults with physical frailty & sarcopenia (PF&S). Here, we describe the procedures fol...
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Rationale: Bimagrumab is a fully human monoclonal antibody that blocks the activin type II receptors, preventing the activity of myostatin and other negative skeletal muscle regulators. Objectives: To assess the effects of bimagrumab on skeletal muscle mass and function in patients with COPD and reduced skeletal muscle mass. Methods: Sixty-sev...
Article
Digital technologies are transforming healthcare and will provide the basis for more patient-centric innovation in the pharmaceutical industry. Digital endpoints in clinical studies have the potential to drive innovation and reduce costly late-stage failures. This is also currently under consideration by regulatory agencies, such as the US Food and...
Article
Background Bimagrumab is a human monoclonal antibody inhibitor of activin type II receptors (ActRII), with anabolic action on skeletal muscle mass by blocking binding of myostatin and other negative regulators of muscle growth. Bimagrumab is under evaluation for muscle wasting and associated functional loss in hip fracture and sarcopenia, and in ob...
Data
Table 1. Primer sequences for the custom real‐time PCR (PrimerDesign Ltd) designed to support the MIQE guidelines: minimum information for publication of quantitative real‐time PCR1 Table 2. Donor patient characteristics of the human primary myoblast
Article
Establishment of an ICD-10-CM code for sarcopenia in 2016 was an important step towards reaching international consensus on the need for a nosological framework of age-related skeletal muscle decline. The International Conference on Frailty and Sarcopenia Research Task Force met in April 2017 to discuss the meaning, significance, and barriers to th...
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Background: Sarcopenia is defined as the age-related loss of skeletal muscle mass and function. While all humans lose muscle with age, 2-5% of elderly adults develop functional consequences (disabilities). The aim of this study was to investigate muscle myogenesis in healthy elderly adults, with or without sarcopenia, compared with middle-aged con...
Article
This letter comments on the letter by Kwang-il Kim.
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There is a growing body of evidence that links nutrition to muscle mass, strength and function in older adults, suggesting that it has an important role to play both in the prevention and management of sarcopenia. This review summarises the discussions of a working group [ESCEO working group meeting 8th September 2016] that met to review current ev...
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Objectives: To assess the effects of bimagrumab on skeletal muscle mass and function in older adults with sarcopenia and mobility limitations. Design: A 24-week, randomized, double-blind, placebo-controlled, parallel-arm, proof-of-concept study. Setting: Five centers in the United States. Participants: Community-dwelling adults (N = 40) aged...
Article
Background: Skeletal muscle is a key mediator of insulin resistance. Bimagrumab, an antibody against activin receptor type II (ActRII), prevents binding of negative muscle regulators, like myostatin, and increases lean mass and decreases fat mass in animal models. Objective: We hypothesized that an improving body composition in insulin resistant...
Article
Background and purpose: Low insulinlike growth factor 1 (IGF1) has been associated with increased risk of atherosclerosis and atrial fibrillation in crosssectional studies. Yet, prospective data linking IGF1 levels to the development of ischemic stroke remain inconclusive. We examined prospectively the association between serum IGF-1 levels and in...
Article
Background: Hypophosphatasia (HPP) is a rare genetic disorder resulting in variable alterations of bone formation and mineralization that are caused by mutations in the ALPL gene, encoding the tissue-nonspecific alkaline phosphatase (ALP) enzyme. Methods: In this phase IIA open-label, single-center, intra-patient, dose-escalating study, adult pa...
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The sustainability of health and social care systems is threatened by a growing population of older persons with heterogeneous needs related to multimorbidity, frailty, and increased risk of functional impairment. Since disability is difficult to reverse in old age and is extremely burdensome for individuals and society, novel strategies should be...
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The exploration of frailty as a pre-disability geriatric condition represents one of the most promising research arenas of modern medicine. Frailty is today indicated as a paradigmatic condition around which the traditional healthcare systems might be re-shaped and optimized in order to address the complexities and peculiarities of elders. Unfortun...
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We have observed over the last 15 years a wide debate both in the medical scientific community and in the public health arena on the definition and operationalization of frailty, typically a geriatric condition, and in particular of physical frailty linked to sarcopenia. Because physical frailty in its initial phase can still be reversed, fighting...
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In the present article, the rationale that guided the operationalization of the theoretical concept of physical frailty and sarcopenia (PF&S), the condition of interest for the "Sarcopenia and Physical Frailty in Older People: Multicomponent Treatment Strategies" (SPRINTT) trial, is presented. In particular, the decisions lead to the choice of the...
Data
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Muscle wasting in old age or cancer may result from failed myofiber regeneration and/or accelerated atrophy. This study aimed to determine from transcriptomic analysis of human muscle the integrity of the cellular stress response system in relation to satellite cell differentiation or apoptosis in patients with cancer (weight‐stable (CWS) or weight...
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Muscle wasting in old age or cancer may result from failed myofiber regeneration and/or accelerated atrophy. This study aimed to determine from transcriptomic analysis of human muscle the integrity of the cellular stress response system in relation to satellite cell differentiation or apoptosis in patients with cancer (weight‐stable (CWS) or weight...
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Muscle atrophy occurs as a consequence of a number of conditions, including cancer, chronic obstructive pulmonary disease (COPD), diabetes mellitus, heart failure, and other chronic diseases, where it is generally a predictor of poor survival. It also occurs as a consequence of disuse and an age-related loss of muscle mass and strength (sarcopenia)...
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Sarcopenia and frailty often co-exist and both have physical function impairment as a core component. Yet despite the urgency of the problem, the development of pharmaceutical therapies for sarcopenia and frailty has lagged, in part because of the lack of consensus definitions for the two conditions. A task force of clinical and basic researchers,...
Article
Leptin is a major adipokine that regulates weight balance and energy homeostasis. There is inconsistent evidence linking circulating leptin levels to risk of stroke. We tested the hypothesis that leptin levels are associated with risk of incident stroke in an elderly community based sample. Serum leptin levels were assayed in 757 strokefree individ...
Article
Background Bimagrumab is a monoclonal antibody that inhibits ligand binding to the activin receptor IIA/B thereby stimulating muscle growth. In a proof of concept study, bimagrumab increased thigh muscle volume (TMV) by 6.5% (p=0.024) and decreased intramuscular adipose tissue (IMAT) by 3% (p=n.s.) after 8 weeks of treatment. Objectives Using quali...
Article
Background: Insulin-like growth factor 1 (IGF-1), reduces progression of atherosclerosis and in cross-sectional studies low circulating IGF-1 is associated with increased carotid intima-media thickness. Yet, prospective data linking IGF-1 levels to development of stroke remain sparse and inconsistent. We related circulating IGF-1 levels to risk of...
Article
Background: Leptin is a major adipokine that regulates weight balance and energy homeostasis. There is some inconsistent evidence linking circulating leptin levels to risk of stroke. We tested the hypothesis that leptin levels are associated with risk of first ever stroke in an elderly community-based population. Methods: Serum leptin levels were a...
Article
Objective: To study activin signaling and its blockade in sporadic inclusion body myositis (sIBM) through translational studies and a randomized controlled trial. Methods: We measured transforming growth factor β signaling by SMAD2/3 phosphorylation in muscle biopsies of 50 patients with neuromuscular disease (17 with sIBM). We tested inhibition...
Article
Skeletal muscle weakness is a leading cause of mobility disability in the elderly (sarcopenia), as a complication of acute or chronic illness (cachexia), and due to inherited or acquired muscle diseases (muscular dystrophies, myositides, etc.). As of now, there are no approved drugs that can reliably increase muscle strength and function. However,...
Article
Objective Muscle loss and metabolic changes occur with disuse [i.e. bed rest (BR)]. We hypothesized that BR would lead to a metabolically unhealthy profile defined by: increased circulating tumor necrosis factor (TNF)-α, decreased circulating insulin-like-growth-factor (IGF)-1, decreased HDL-cholesterol, and decreased muscle density (MD; measured b...
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To relate serum insulin-like growth factor-1 (IGF-1) to risk of Alzheimer disease (AD) dementia and to brain volumes in a dementia-free community sample spanning middle and older ages. Dementia-free Framingham participants from generation 1 (n = 789, age 79 ± 4 years, 64% women) and generation 2 (n = 2,793, age 61 ± 9 years, 55% women; total = 3,58...
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Cachexia affects the majority of patients with advanced cancer and is associated with a reduction in treatment tolerance, response to therapy, and duration of survival. One impediment towards the effective treatment of cachexia is a validated classification system. 41 patients with resectable upper gastrointestinal (GI) or pancreatic cancer underwe...
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To determine the cardiometabolic risks of testosterone and growth hormone (GH) replacement therapy to youthful levels during aging. A double-masked, partially placebo controlled study in 112 men 65-90 years-old was conducted. Transdermal testosterone (5 g vs. 10 g/day) using a Leydig Cell Clamp and subcutaneous recombinant GH (rhGH) (0 vs. 3 vs. 5...
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Sarcopenia, the age-related skeletal muscle decline, is associated with relevant clinical and socioeconomic negative outcomes in older persons. The study of this phenomenon and the development of preventive/therapeutic strategies represent public health priorities. The present document reports the results of a recent meeting of the International Wo...
Article
Low vitamin B-6 status, based on plasma concentrations of pyridoxal-5-phosphate (PLP), has been identified in inflammatory diseases, including cardiovascular disease, rheumatoid arthritis, inflammatory bowel disease, and diabetes. Our objective was to examine the association between plasma PLP and multiple markers of inflammation in a community-bas...
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Skeletal muscle dysfunction is a prevalent and clinically important systemic manifestation of chronic obstructive pulmonary disease (COPD) that predicts morbidity and mortality. Skeletal muscle retains its plasticity in response to anabolic stimuli such as exercise in COPD and is therefore a promising target for novel pharmacological therapies aime...
Article
Polyunsaturated fatty acids (PUFAs) may influence bone health. The objective of this work was to examine associations between plasma phosphatidylcholine (PC) PUFA concentrations and hip measures: (1) femoral neck bone mineral density (FN-BMD) (n = 765); (2) 4-year change in FN-BMD (n = 556); and (3) hip fracture risk (n = 765) over 17-year follow-u...
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Full-text available
Sarcopenia, the age-related skeletal muscle decline, is associated with relevant clinical and socioeconomic negative outcomes in older persons. The study of this phenomenon and the development of preventive/therapeutic strategies represent public health priorities. The present document reports the results of a recent meeting of the International Wo...
Chapter
There are many different types of arthritis, which, broadly defined, can be categorized into two major groups: degenerative and inflammatory. Osteoarthritis (OA) is the most common type of degenerative arthritis. In an inflammatory arthritis such as rheumatoid arthritis (RA) there is a systemic illness with inflammation of many joints. There is evi...
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A first Task Force on Sarcopenia was organized in Castres, near Toulouse, in 2008, with a series of papers on Sarcopenia published in the JNHAin 2009. Folowing this work a second international task force on Sarcopenia was organized in Rome in 2009 and the consensus paper was published in the JAMDA. Our third international Task Force was hosted in A...
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We hypothesized that treatment with testosterone (T) and recombinant human growth hormone (rhGH) would increase lean mass (LM) and muscle strength proportionally and an in a linear manner over 16 weeks. This was a multicenter, randomized, controlled, double-masked investigation of T and rhGH supplementation in older (71 ± 4 years) community-dwellin...
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Acute deviations in protein intake before the quantification of protein kinetics in older humans may explain the controversy over the effects of older age on muscle protein synthesis and proteolysis rates. We hypothesized that an acute decrease in protein intake from the habitual intake is associated with lower muscle protein synthesis and higher p...
Article
A consensus conference convened by the Society of Sarcopenia, Cachexia and Wasting Disorders has concluded that "Sarcopenia, ie, reduced muscle mass, with limited mobility" should be considered an important clinical entity and that most older persons should be screened for this condition. "Sarcopenia with limited mobility" is defined as a person wi...